© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 8, 582,
April 18, 2001
© 2001 Oxford University Press
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Scientists Report New Finding in Development of B Cells
In the early 1990s, scientists reported that interleukin 10, a signaling protein excreted by activated immune cells, was essential for the maturation of B lymphocytes. That is, add IL-10 in culture, and naive, undifferentiated B cells mature; deprive the cells of the protein, and no differentiation occurs.
But, as often happens in science, even the most straightforward discoveries turn out not to be so straightforward. In the March 15 issue of the journal Blood, scientists report for the first time that another protein called TIMP-1 seems to switch on the expression of IL-10 in normal B cells and B-cell non-Hodgkin’s lymphoma.
Maryalice Stetler-Stevenson, Ph.D., a scientist at the National Cancer Institute and senior author on the paper, said this finding is noteworthy because many previous studies of IL-10 almost certainly involved cells and/or serum that contained TIMP-1. "Perhaps some of the biological effects that have been associated with IL-10 are, in fact, driven by TIMP-1," she said. "Until now, there was no reason even to consider this possibility."
Stetler-Stevenson noted that the finding could have important clinical implications. She said the group showed that high TIMP-1 levels were found in severe, or high-grade, B-cell lymphomas, while the protein was undetectable or nearly absent in the low-grade cancers. The authors say this further supports previous reports of poor prognoses for B-cell non-Hodgkin lymphomas that express high levels of IL-10.
According to Liliana Guedez, Ph.D., an NCI scientist and lead author on the study, she and her colleagues are now following up the current finding with additional studies of TIMP-1’s control of other interleukins that are involved in B-cell maturation and survival. They are also exploring the correlation between high and low TIMP-1 levels in lymphoma.
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